Myocyte enhancer factors 2 (MEF2) is a family of
muscle-enriched transcription factors that have an essential role in myogenesis. In
addition, MEF2 is also expressed at high levels in neurons
and lymphocytes, where it serves as a regulator of neuronal and immune cell
differentiation and function [1], [2].

MEF2 is necessary for the transcriptional activation of
Interleukin 2 (IL-2) (and possible other cytokines) during
peripheral T cell activation [3]. It plays a crucial role in T-lymphocyte
apoptosis by regulating expression of Nuclear receptor subfamily 4, group A, member 1
(NUR77) [4], [5].

To date, four MEF2 proteins have been identified:
MEF2A, MEF2B,
MEF2C, and MEF2D, which are
expressed in distinct, but overlapping patterns during embryogenesis, and in adult
tissues. MEF2 proteins form homo- and heterodimers that
constitutively bind to response elements [2].

Association of MEF2 with
HDAC4, HDAC5,
HDAC7 and HDAC9 results in
deacetylation of nucleosomal histones surrounding MEF2
DNA-binding sites, with subsequent suppression of
MEF2-dependent genes. Calcium/calmodulin-dependent protein
kinases I and IV (CaMK I and CaMK
IV) phosphorylate HDACs, creating docking
sites for a chaperone protein 14-3-3. Upon binding of
14-3-3, HDACs are released from
MEF2 and transported (except
HDAC9) to the cytoplasm via a C-terminal nuclear export
sequence. Once released from associated repressors, MEF2 is
bound by the p300 co-activator [2].

Calcium-bound Calmodulin 2 (Calmodulin) also associates
with and activates Protein phosphatase 3 (formerly 2B), catalytic subunits
(Calcineurin A (catalytic)). Calcineurin A
(catalytic) dephosphorylates NF-AT1(NFATC2)
leading to its translocation into the nucleus. In the nucleus
NF-AT1(NFATC2) directly associates with
MEF2A and MEF2D and recruits
p300 co-activator to MEF2
target genes [2]. Upon T cell activation, a subpopulation of
Calcineurin A (catalytic) translocates into the nucleus to
maintain the transcriptional activity of NF-AT1(NFATC2) and
other factors [6].

In response to increased intracellular Ca('2+),
Calmodulin is activated and associated with the
MEF2-binding region of CABIN1,
releasing MEF2 so that it can associate with
NF-AT1(NFATC2)-p300 complexes
and activate target gene expression.

CABIN1 also associates with and represses
Calcineurin A (catalytic), and thus inhibits
MEF2 activity by inhibiting an upstream activator of
MEF2-dependent transcription.

Terms of Use of Thomson Reuters (Scientific) Inc. Maps. All users agree that (a) no right, title or interest in the Maps is transferred by display of the Maps; (b) the Maps may only be used for purposes of determining whether to purchase Bio-Rad products and services displayed in relation to the Maps; (c) the Maps may not be copied, printed, downloaded, modified or disassembled, and no derivatives of the Maps may be created; (d) the Maps and the data contained in the Maps may not be used for purposes of development or commercialization of any third party product or service without first obtaining a separate written license for such use from Thomson Reuters (Scientific) Inc.